This study will readily, quickly and efficiently evaluate whether lower prenatal and early life vitamin D levels can explain, at least in part, the higher rates of allergic disease outcomes among African American children compared with White children. Pediatric allergy and asthma are a considerable public health burden, even more so among African Americans, and there are no proven prevention strategies. Further, there is an epidemic of vitamin D deficiency caused by changes in lifestyles in westernized cultures, including the United States, which disproportionately affects African Americans compared to lighter skinned individuals. Vitamin D deficiency is a compelling candidate as a contributor to increased risk for allergic disorders and is of great current interest. This proposed study will investigate the associations between multiple serological levels of vitamin D (25(OH)D) and the outcomes of skin prick testing (SPT) and total and specific serum IgE (sIgE) concentration, as well as wheeze and doctor-diagnosed atopic dermatitis at age 2 years in an already established racially diverse birth cohort. We have not located any published research in which prenatal, cord and early life (ages 6 months and 1 and 2 years) serological levels of 25(OH)D are incorporated into a single analysis of allergic outcomes as proposed here. The samples for vitamin D (25(OH)D) analyses are already at hand in an institutional biorepository, and the outcomes have been ascertained by physician exam. There are clear biological mechanisms that explain how prenatal and early life vitamin D levels may affect fetal immune development and risk of allergic disease. Previous human studies examining these effects have been notably limited by the use of dietary vitamin D quantification (food frequency questionnaires) without biomarkers, predominantly White populations, subjective outcomes and sub-optimal statistical approaches. The ongoing, predominantly African American (62%) NIH-funded birth cohort study WHEALS will be used for this application. The Specific Aims are to determine the degree to which early life 25(OH)D levels (prenatal, cord, 6 months and 1 and 2 years of age) account for the worse outcomes experienced by African American children compared with White children with respect to the following: 1) an increased likelihood of having a positive allergen skin prick test or elevated sIgE test; 2) higher levels of total IgE; 3) higher rates of atopic dermatitis; and, 4) higher rates of wheeze (controlling for other key risk factors such as season). Sample size ranges from 448 to 537 (varies by aim). This proposed study will address the aims by utilizing cutting-edge statistical techniques including propensity scores, structural equation models and latent variables. With the recent controversial IOM report and increased public awareness, this work is highly significant as well as urgent. Vitamin D needs to be evaluated rigorously as it is modifiable and can potentially provide a low cost public health intervention that could help prevent clinical allergy and asthma and reduce racial disparities. PUBLIC HEALTH RELEVANCE: African American children are more likely than White children to have allergic diseases and to wheeze. Social economic status cannot fully explain these differences. We seek to examine whether early life vitamin D levels can explain these racial differences in a study in the Detroit, Michigan area.